Toll-like receptors differentially induce nucleosome remodelling at the IL-12p40 promoter

Inka Albrecht, Thomas Tapmeier, Stefan Zimmermann, Markus Frey, Klaus Heeg, Alexander Dalpke

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFα. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.

Original languageEnglish
Pages (from-to)172-177
Number of pages6
JournalEMBO Reports
Volume5
Issue number2
DOIs
Publication statusPublished - 1 Feb 2004
Externally publishedYes

Keywords

  • immunology
  • dendritic cell (DC)
  • TLR signaling

Cite this